Cytomegalovirus upregulates vascular endothelial growth factor and its second cellular kinase domain receptor in human fibroblasts.

Abstract Human cytomegalovirus (HCMV) activation and elevated levels of vascular endothelial growth factor (VEGF) have been found to be associated with transplant rejection. However, information is lacking about whether elevated levels of this multifunctional factor are directly due to viral activation, or if they derive from impurities within the culture supernatant of infected cell cultures. We used purified as well as unpurified viral stocks to infect human fibroblasts in vitro and applied PCR, Western blot, ELISA, and immunofluorescence staining to investigate the expression of VEGF and its receptors. Our data suggest that HCMV infection triggers an early and sustained induction of VEGF and kinase insert domain receptor (KDR) mRNAs, whereas transcript levels of FLT-1 remain unchanged by viral infection. Analysis of the extracellular VEGF and cellular KDR protein expression after infection with purified and unpurified HCMV strains AD169 and TOLEDO showed, in clear contrast to UV-inactivated virus prepa...